Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality; however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: (1) define the role of Hepatitis C viral response to pegylated interferon-based therapy (2) evaluate novel therapeutic strategies in the management of Hepatitis C virus among HIV co-infected individuals, and (3) develop novel genomic and proteomic markers that predict Hepatitis C viral response to existing and newer therapies. Analyses of the kinetics of the viral response to Hepatitis C therapy in Hepatitis C/HIV co-infected individuals suggest that it may be possible to predict long term response to anti-Hepatitis C therapy based on the initial response of the level of Hepatitis C virus in the plasma. Using combination therapy of pegylated interferon together with ribavirin in these subjects, we are determining whether genomic and proteomic markers can predict response to therapy prior to initiation of treatment. Another clinical trial will determine whether more frequent doses of pegylated interferon in combination with ribavirin can enhance the viral kinetic response to Hepatitis C therapy in persons with Hepatitis C infection and HIV infection. A new clinical trial using albumin-conjugated interferon alpha (Albuferon) to treat Hepatitis C among HIV infected patients will begin enrollment later this year.